The nucleus accumbens (Acb) is a key neural substrate underlying goal-directed behaviors for both drugs of abuse as well as 'natural' rewards. Here, I review electrophysiological and electrochemical studies completed in our laboratory that examined Acb cell firing and rapid dopamine signaling during behaviors directed toward reward procurement. Electrophysiological studies are reviewed showing that Acb neurons exhibit patterned discharges relative to operant responding for intravenous self-administration of cocaine versus 'natural' reinforcement in rodents. Importantly, subsequent studies showed that discrete subsets of Acb neurons are selectively activated during multiple schedules for a natural reward (water or food) versus cocaine self-administration. These later findings indicate that separate neural circuits selectively process information about goal-directed behaviors for cocaine versus natural reward. In addition, recent findings are reviewed showing that reinforcer selective firing of Acb neurons is not a direct consequence of chronic drug exposure. Next, electrochemical studies are summarized that used fast scan cyclic voltammetry to measure rapid (subsecond) changes in dopamine in the Acb during cocaine self-administration as well as 'natural' reinforcement in rodents. These findings are considered with respect to the role of dopamine in modulating the activity of Acb neurons that encode goal-directed behaviors, the functional organization of the Acb on a microcircuit level, and proposed directions for future studies.